1. Field of the Invention
The present invention relates generally to methods and devices useful to identify the presence of an analyte in a sample.
2. Background Information
Surface-enhanced Raman scattering (SERS) is a sensitive spectroscopic method for detection of an analyte. Raman Spectroscopy probes vibrationally excitable levels of an analyte. Once a vibrational level is excited by a photon, the energy of the photon shifts by an amount equal to that of the level (Raman scattering). A Raman spectrum, similar to an infrared spectrum, consists of a wavelength distribution of bands corresponding to molecular vibrations specific to the sample being analyzed (the analyte). In the practice of Raman spectroscopy, the beam from a radiation source is focused upon the sample to thereby generate inelastically scattered radiation, which is optically collected and directed into a wavelength-dispersive spectrometer in which a detector converts the energy of impinging photons to electrical signal intensity. In SERS, analyte molecules are adsorbed on noble metal nanoparticles. These nanoparticles, once excited by light, set up plasmon modes, which, in turn, create near fields around each particle. These fields can couple to analyte molecules in the near field regions. As a result, concentration of the incident light occurs at close vicinity of the nanoparticles enhancing the Raman scattering from the analyte molecules. This method can enhance the detection of biological systems by as much as a factor of 1014.
Multiplexing is a demanding approach for high throughput assays in various areas such as biological research, clinical diagnosis and drug screening because of its great potentials in increasing efficiencies of chemical and biochemical analyses. In a multiplex assay, multiple probes are used that have specificities to corresponding analytes in a sample mixture. One of the critical challenges in establishing a multiplex platform is to develop a probe identification system that has distinguishable components for each individual probe in a large probe set.
Previous methods have utilized SERS in combination with multiplex analysis. Such methods utilize target-coated gold particles and DNA probes co-modified with both a Raman dye and thiol group (Cao et al, Science 297: 1536). However, such reagents are generally expensive to manufacture and labor intensive to use. In addition, coupling the Raman dye and thiol group to the analyte does not provide flexibility in application and/or removal of the dye or SERS substrate. Thus, there exists a need for compositions and methods that provide lower costs and increased flexibility in labeling analytes and capture reagents during multiplex analysis.
The following detailed description contains numerous specific details in order to provide a more thorough understanding of the disclosed embodiments of the invention. However, it will be apparent to those skilled in the art that the embodiments can be practiced without these specific details. In other instances, devices, methods, procedures, and individual components that are well known in the art have not been described in detail herein.